Dissociation of β-Sheet Stacking of Amyloid β Fibrils by Irradiation of Intense, Short-Pulsed Mid-infrared Laser

Takayasu Kawasaki, Toyonari Yaji, Toshiaki Ohta, Koichi Tsukiyama, Kazuhiro Nakamura

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Structure of amyloid β (Aβ) fibrils is rigidly stacked by β-sheet conformation, and the fibril state of Aβ is profoundly related to pathogenesis of Alzheimer’s disease (AD). Although mid-infrared light has been used for various biological researches, it has not yet been known whether the infrared light changes the fibril structure of Aβ. In this study, we tested the effect of irradiation of intense mid-infrared light from a free-electron laser (FEL) targeting the amide bond on the reduction of β-sheet content in Aβ fibrils. The FEL reduced entire contents of proteins exhibiting β-sheet structure in brain sections from AD model mice, as shown by synchrotron-radiation infrared microscopy analysis. Since Aβ1-42 fibril absorbed a considerable FEL energy at amide I band (6.17 μm), we irradiated the FEL at 6.17 μm and found that β-sheet content of naked Aβ1-42 fibril was decreased using infrared microscopic analysis. Consistent with the decrease in the β-sheet content, Congo-red signal is decreased after the irradiation to Aβ1-42 fibril. Furthermore, electron microscopy analysis revealed that morphologies of the fibril and proto-fibril were largely changed after the irradiation. Thus, mid-infrared light dissociates β-sheet structure of Aβ fibrils, which justifies exploration of possible laser-based therapy for AD.

Original languageEnglish
Pages (from-to)1039-1049
Number of pages11
JournalCellular and Molecular Neurobiology
Volume38
Issue number5
DOIs
Publication statusPublished - 1 Jul 2018

Keywords

  • Alzheimer’s disease
  • Amyloid fibril
  • Mid-infrared free-electron laser
  • β-sheet

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